Rattle Snake Toxicity


Article Author:
Virat Patel


Article Editor:
Richard Hamilton


Editors In Chief:
David Tauber


Managing Editors:
Avais Raja
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Carrie Smith
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James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/6/2019 12:27:06 AM

Introduction

Rattlesnakes are found throughout the Americas and include snakes in the genera Crotalus and Sistrurus. They are also known as pit vipers, lanceheads, and Asian pit vipers (genus Trimeresurus). Their primary defense mechanism is to hide, and then rattle and hiss which are meant to scare predators away. When they are further challenged, they bite and envenomate with potentially deadly effects. Knowing the common snakes in your area is important in managing a snake bite appropriately.

Etiology

The morbidity and mortality associated with snake bites are usually due to the envenomation. Snake bite wounds usually do not get infected due to the relatively inhibitory effect of the venom on microorganisms. Humans often get bit by stepping on snakes mistakenly or by getting extremely close to them when they are in hiding. Usually, the rattle gives away their presence, but there have been rattlesnakes noted to have a dysfunctional tail, possibly a population selected by humans that kill rattling snakes in highly populated areas. Most deaths related to snake bites are due to immediate anaphylactic reactions or failure to seek medical attention for anti-venom administration. Snakebite is a common complication resulting from improper handling or interaction with snakes for leisure. Unfortunately, it is also common in professional snake handlers. [1]

Epidemiology

The mortality rate is higher with rattlesnake bites compared to all snake bites. In the United States, approximately 9,000 people per year suffer a snake bite, but only five deaths occur. Interestingly, poison center data shows that one in 736 patients who suffer a rattlesnake bite die. Rattlesnakes are found in varying climates in both North and South America.[2]

Pathophysiology

The symptoms from a snake bite are related to the envenomation. Rattlesnakes have hollow fangs in the anterior mouth that inject venom into subcutaneous tissue. Rarely, intravenous injection occurs, but when it does, it is usually deadly. Crotalid venom causes necrosis due to toxic tissue enzymes. It also causes increased permeability of the cell membrane, which leads to an increased spread of the venom locally. Crotalid venom has a fibrinolytic and protein C activation effect causing coagulopathy in patients. Certain rattlesnakes, such as timbers, have a higher incidence of angioedema. The mechanism by which angioedema associated with timber rattlesnake envenomation occurs is not understood. The incidence of angioedema in patients suffering from timber rattlesnake bites is high and found to be 66% in one study.

Toxicokinetics

There are two neurotoxins found in rattlesnakes. One is an enzyme phospholipase A2 which decreases the LD50 of rattlesnake venom by ten to 80 times, and the other is canebrake toxin. Both of these toxins inhibit neuromuscular transmission by blocking Ca2+ channels on the presynaptic side of the neuromuscular junction. This may lead to paralysis of a muscle group if it is present in high concentrations. This toxin is also found to induce myokymia, which is an involuntary quivering of muscles or muscle fibers in localized areas.

History and Physical

Rattlesnake bite victims may present with a variety of local and systemic symptoms. Local symptoms include pain and swelling around the bite site, bleeding from the bite site, and local tissue necrosis and ecchymosis. Systemic symptoms include angioedema, bleeding from other orifices including hematemesis and hematochezia, nausea, vomiting, diarrhea, dyspnea, and anaphylaxis.[3]

Evaluation

Initial labs are necessary for all snake bites and should include coagulation studies, hemoglobin, platelets, and fibrinogen. While an x-ray of the bite wound is not necessary, it may be prudent if there is a suspicion of a foreign body or a fracture that may have occurred while escaping the snake. Upon initial evaluation, the leading edge of the swelling and redness surrounding the bite site should be marked. Grading the envenomation determines the use of antivenin.

Minimal Envenomation (no antivenin)

  • Swelling, pain, and ecchymosis limited to the site of the bite
  • No systemic signs
  • Normal coagulation parameters or isolate mild alterations without clinically relevant bleeding

Moderate Envenomation

  • Swelling, pain and ecchymosis involving less than full extremity or extending < 50 cm in adults
  • Systemic symptoms present, such as vomiting, mild hypotension, mild tachycardia
  • Abnormal coagulation parameters without clinically relevant bleeding

Severe Envenomation

  • Swelling, pain, and ecchymosis involving an entire extremity (or more) or threatening airway
  • Systemic signs including altered mental status and hemodynamic instability
  • Abnormal coagulation parameters with clinically relevant bleeding

Treatment / Management

Appropriate management should begin in the pre-hospital setting. Facilitate immediate andrapid transport of the patient for evaluation by a qualified medical provider. Immobilize the extremity to reduce the potential dissemination of venom through the lymphatic system, but this should not delay transport. Patients presenting with a snake bite should be stabilized by initially assessing their airway, breathing, and circulation just like any other trauma presentation. Some patients may be able to identify the snake that bit them, but this may not always be accurate. Knowing the common snakes in the locality of the patient may help elucidate the likely culprit. In any case, the treatment algorithm for snake envenomation does not change drastically depending on the snake.[4][5][6][7]

Please refer to the management algorithm attached for a step-by-step approach to crotaline envenomation.

The leading edge of the swelling and redness surrounding the bite site should be marked and tracked every 15 min-30 min. The extremity should be immobilized to reduce motion, and pain should be treated with IV opioids if necessary. Initial labs are necessary for all snake bites and should include coagulation studies, hemoglobin, platelets, and fibrinogen. Tetanus should be updated if necessary, and the local poison center should be notified.

Signs of envenomation may vary between presentations but should be assessed in all snake bite victims. Systemic signs include hypotension, bleeding or oozing from IV sites, vomiting, diarrhea, angioedema and neurotoxicity. Assessment for facial edema including tongue swelling and respiratory distress should be recognized, and a definitive airway should promptly be obtained if there are concerns for airway compromise.

A patient with minimal signs of envenomation should be monitored for at least eight hours and should get a repeat coagulation panel before discharge.

Crotalidae polyvalent immune Fab (CroFab) Dosing

Initial bolus four to six vials mixed in 250 mL normal saline (NS) administered over one hour (same number of vials in less fluid for children). Initiate treatment with a bolus of 10 mL/hr observing for adverse effects. If none, then increase every few minutes to achieve complete administration in one hour. Observe patient for local swelling and systemic symptoms. If signs of progression then repeat with four to six vials over one hour.  Do not administer to normalize abnormal coagulation markers. Repeat until initial control is achieved (local swelling improves or stops, resolution of systemic signs, and resolution of clinically relevant bleeding. After achieving control, maintenance doses of two vials every six hours for 18 hours are recommended for rattlesnakes, patients with a coagulopathy, and those with severe clinical envenomations. This is not usually required for moderate copperhead envenomations. Remember that if recurrent swelling or coagulopathy occurs during maintenance doses, reduce with bolus protocol.

Recheck coagulation labs prothrombin time (PT), fibrinogen, platelets, and hemoglobin at day two to three and days five to seven. Recurrent coagulopathy without clinically significant bleeding has been observed. Some retreat and others follow parameters to normalization. 

Consider contacting a Poison Control Center to discuss with a medical toxicologist. 

Pearls and Other Issues

Progression of angioedema is unpredictable as it may progress beyond presentation or may start regressing soon after presentation.[8] Elevated protime and/or decreased platelets and fibrinogen levels are also signs of envenomation. Coagulopathy responds to antivenin treatment, but the thrombocytopenia may persist.[9] Life-threatening bleeding is rare despite severe coagulopathy and thrombocytopenia. Platelet or fresh frozen plasma (FFP) transfusion should be avoided except when there is life-threatening bleeding because antivenin is the definitive treatment.

If no signs of envenomation are present, the patient should be observed for at least six hours, and labs should be repeated before discharge. If the patient develops signs during the observation period or presents with signs of envenomation, erythema and swelling should be marked, measured, and tracked for progression. Prophylactic antibiotics are not indicated for snake bites as they have an extremely low likelihood of infection owing to the proteolytic properties of snake venom.

Overall Indications for Crotalidae polyvalent immune Fab (CroFab) 

  • Indicated for moderate or severe envenomations only, not minimal
  • Swelling that is progressing and is more than minimal
  • Any systemic symptoms
  • Any coagulopathy such as increased protime, or decreased platelet count or fibrinogen

CroFab will help local symptoms and coagulopathy, and local symptoms are used to monitor response to therapy. Cessation in the progression of swelling and erythema is reassuring.

Worsening angioedema is not a sign of the failure of treatment with CroFab. CroFab is not expected to reduce or stop the progression of angioedema. Typically, the angioedema resolves with supportive care.

Coagulation studies will improve with CroFab treatment, but persistent thrombocytopenia has been noted despite CroFab treatment and is not considered the failure of treatment. Other systemic signs are expected to improve with treatment as well. Local swelling and pain may persist for weeks to months despite CroFab therapy. CroFab is contraindicated in a patient with known allergy to sheep protein. CroFab use is associated with an 8% incidence of immediate hypersensitivity and a 13% incidence of serum sickness (which is rare and almost always clinically insignificant).

Enhancing Healthcare Team Outcomes

The diagnosis and management of rattlesnake bite is best done with a multidisciplianry team that includes the emergency department physician, toxicologist, poison control, surgeon, internist and an intensivist. Appropriate management should begin in the pre-hospital setting. Facilitate immediate and rapid transport of the patient for evaluation by a qualified medical provider. Immobilize the extremity to reduce the potential dissemination of venom through the lymphatic system, but this should not delay transport. Patients presenting with a snake bite should be stabilized by initially assessing their airway, breathing, and circulation just like any other trauma presentation. All patients must be monitored by the nurse until stable. Those who are asymptomatic may be discharged after a period of observation. Those with signs of envenomation need admission to the ICU for close clinical and biochemical monitoring.[10][11][4]

The prognosis for patients treated promptly is good.

 

 


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    Contributed by Virat Patel, MD
Attributed To: Contributed by Virat Patel, MD

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Rattle Snake Toxicity - Questions

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The practice of pressure immobilization for a snake bite is not recommended for envenomation by which snake?



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A patient is brought to the emergency department after being bitten by a snake on his left ankle in North Carolina. He brings a picture of the snake that bit him. It has been 90 minutes since suffering the snake bite. The patient complains of hoarseness as well as pain and swelling at the bite site. Vital signs are as follows: temperature 37.4 C, heart rate 110 bpm, blood pressure 80/50 mmHg, respirations 18 per minute, pulse oximetry 99% on room air. The physical exam is notable for two puncture marks on the posterior left ankle with surrounding swelling and ecchymosis. There is no active bleeding from the puncture site but there is significant tenderness surrounding the site. Tongue and lip swelling are noted and the oropharynx cannot be visualized. Lungs are clear to auscultation. He has no medical problems and does not take any medications. The patient has 2 large bore IVs. What is the next best step in management?

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    Contributed by John White; Virginia Herpetological Society
Attributed To: Contributed by John White; Virginia Herpetological Society



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A 6-year-old female was playing in the woods with her friends in western North Carolina is bitten by a snake. The parents bring her to the emergency department for evaluation immediately. They do not know snake's identity. Physical shows normal vital signs, two puncture wounds in the left ankle with minimal surrounding ecchymosis and mild swelling. Otherwise, the patient appears to be in a usual state of health with normal airway, breathing, and circulation. Coagulation panel is normal. What is the best next step in management?



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A 17-year-old male was camping in the woods of South Carolina when he came across a snake. He grabbed the snake by the tail in an attempt to scare a friend. He was bitten on the right hand. Friends identify the snake as a copperhead. By the time he arrives at the emergency department, the hand is remarkably swollen, the patient is wheezing, and has diffuse hives. He is using accessory muscles to breath. There is no perioral or lip swelling. Vital signs are blood pressure 90/60 mmHg, heart rate 110 bpm, respiratory rate 24/min, pulse oximetry 92% on room air, and temperature 98.9 F. The patient is placed on a non-rebreather mask, two large bore IV accesses are obtained, and the patient is placed on a monitor. One liter of normal saline is ongoing. What is the next best step in management?



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Rattle Snake Toxicity - References

References

Snakebite injuries treated in United States emergency departments, 2001-2004., O'Neil ME,Mack KA,Gilchrist J,Wozniak EJ,, Wilderness & environmental medicine, 2007 Winter     [PubMed]
Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop., Lavonas EJ,Ruha AM,Banner W,Bebarta V,Bernstein JN,Bush SP,Kerns WP 2nd,Richardson WH,Seifert SA,Tanen DA,Curry SC,Dart RC,, BMC emergency medicine, 2011 Feb 3     [PubMed]
Epidemiology of severe and fatal rattlesnake bites published in the American Association of Poison Control Centers' Annual Reports., Walter FG,Stolz U,Shirazi F,McNally J,, Clinical toxicology (Philadelphia, Pa.), 2009 Aug     [PubMed]
Refractory thrombocytopenia despite treatment for rattlesnake envenomation., Gold BS,Barish RA,Rudman MS,, The New England journal of medicine, 2004 Apr 29     [PubMed]
Schaeffer TH,Khatri V,Reifler LM,Lavonas EJ, Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2012 Feb;     [PubMed]
Tanen D,Ruha A,Graeme K,Curry S, Epidemiology and hospital course of rattlesnake envenomations cared for at a tertiary referral center in Central Arizona. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2001 Feb;     [PubMed]
Lefkowitz RY,Taylor J,Balfe D, Reality bites: a case of severe rattlesnake envenomation. Journal of intensive care medicine. 2013 Sep-Oct;     [PubMed]
Rodriguez-Acosta A,Aguilar I, Toxoid preparation from the venom of Crotalus durissus cumanensis (South American rattle snake). The Journal of tropical medicine and hygiene. 1987 Feb;     [PubMed]
Brazil OV, Neurotoxins from the South American rattle snake venom. Taiwan yi xue hui za zhi. Journal of the Formosan Medical Association. 1972 Jul 28;     [PubMed]
Wigginton JB, Snake, rattle, and roll. Journal of the Mississippi State Medical Association. 2013 Mar;     [PubMed]
Moorman CT 3rd,Moorman LS,Goldner RD, Snakebite in the tarheel state. Guidelines for first aid, stabilization, and evacuation. North Carolina medical journal. 1992 Apr;     [PubMed]

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